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Biomedical subjects

S Sardesai

Publications and source records attributed to S Sardesai.

15 recordsLinked to original sources

High frequency ventilation: basic concepts and clinical application.

High frequency ventilation (HFV) is a mode of therapy that improves gas exchange with pressure fluctuations much lower than that required for conventional ventilation. HFV is efficacious in the "rescue" management of infants with respiratory failure. Although each HFV system has functional characteristics that are design related, it now appears that when used with similar treatment strategies and within functional limitations, similar outcomes can be achieved. Ideally, the clinician or the operator should be familiar with the basic concepts of different high frequency ventilators to achieve maximal benefits from using these devices in infants with respiratory failure.

High-Frequency Ventilation↗

Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial.

BACKGROUND: Inhaled nitric oxide improves oxygenation and lessens the need for extracorporeal-membrane oxygenation in full-term neonates with hypoxaemic respiratory failure and persistent pulmonary hypertension, but potential adverse effects are intracranial haemorrhage and chronic lung disease. We investigated whether low-dose inhaled nitric oxide would improve survival in premature neonates with unresponsive severe hypoxaemic respiratory failure, and would not increase the frequency or severity of intracranial haemorrhage or chronic lung disease. METHODS: We did a double-blind, randomised controlled trial in 12 perinatal centres that provide tertiary care. 80 premature neonates (gestational age < or = 34 weeks) with severe hypoxaemic respiratory failure were randomly assigned inhaled nitric oxide (n=48) or no nitric oxide (n=32, controls). Our primary outcome was survival to discharge. Analysis was by intention to treat. We studied also the rate and severity of intracranial haemorrhage, pulmonary haemorrhage, duration of ventilation, and chronic lung disease at 36 weeks' postconceptional age. FINDINGS: The two groups did not differ for baseline characteristics or severity of disease. Inhaled nitric oxide improved oxygenation after 60 min (p=0.03). Survival at discharge was 52% in the inhaled-nitric-oxide group and 47% in controls (p=0.65). Causes of death were mainly related to extreme prematurity and were similar in the two groups. The two groups did not differ for adverse events or outcomes (intracranial haemorrhage grade 2-4, 28% inhaled nitric oxide and 33% control; pulmonary haemorrhage 13% and 9%; chronic lung disease 60% and 80%). INTERPRETATION: Low-dose inhaled nitric oxide improved oxygenation but did not improve survival in severely hypoxaemic premature neonates. Low-dose nitric oxide in the most critically ill premature neonates does not increase the risk of intracranial haemorrhage, and may decrease risk of chronic lung injury.

Administration, Inhalation↗

Aneurysm of the ductus arteriosus: a congenital lesion.

The objective of this study was to evaluate the clinical, radiological, and echocardiographic findings in 11 neonates with aneurysm of ductus arteriosus presented in our institutions between 1993 and 1996, and to postulate a new theory for the pathogenesis of this lesion. Medical records, radiographic studies, and echocardiograms were reviewed. All infants underwent follow-up echocardiograms every 2 to 3 days until the aneurysm spontaneously resolved or surgery was performed. The infants were predominantly term males; six had evidence of fetal distress, two were diagnosed prenatally by fetal echocardiogram, chest X ray evidenced mediastinal mass in six patients. The first echocardiogram showed structurally normal heart with an aneurysmal patent ductus arteriosus. In eight patients the aneurysm completely resolved by 5 to 10 days. One infant underwent surgical resection of the aneurysm after observation for 11 days with no change in size. Thrombosis of the aneurysm was noted in two patients; both underwent surgery. Increasing reports of ductal aneurysms in infants may reflect the availability of high-resolution echocardiography and more frequent use of echocardiography in the neonatal intensive care unit. Spontaneous resolution occurred in the majority of cases as in previous reports. We postulate that, at least in some cases, aneurysm of the ductus arteriosus is a congenital lesion that may represent poststenotic dilation of the ductus due to turbulent flow through a stenotic segment at its pulmonary artery end during fetal life. The presence of aneurysm of the ductus arteriosus should be excluded in selected cases of fetal distress, by fetal echocardiography.

Aortic Aneurysm, Thoracic↗

Randomized, multicenter trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe, persistent pulmonary hypertension of the newborn.

BACKGROUND: Although inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in newborn infants with persistent pulmonary hypertension, its effects are variable. We hypothesized (1) that the response to iNO therapy is dependent on the primary disease associated with persistent pulmonary hypertension of the newborn (PPHN) and (2) that the combination of high-frequency oscillatory ventilation (HFOV) with iNO would be efficacious in patients for whom either therapy alone had failed. METHODS: To determine the relative roles of iNO and HFOV in the treatment of severe PPHN, we enrolled 205 neonates in a randomized, multicenter clinical trial. Patients were stratified by predominant disease category: respiratory distress syndrome (n = 70), meconium aspiration syndrome (n = 58), idiopathic PPHN or pulmonary hypoplasia (excluding congenital diaphragmatic hernia) ("other": n = 43), and congenital diaphragmatic hernia (n = 34); they were then randomly assigned to treatment with iNO and conventional ventilation or to HFOV without iNO. Treatment failure (partial pressure of arterial oxygen [PaO2] < 60 mm Hg) resulted in crossover to the alternative treatment; treatment failure after crossover led to combination treatment with HFOV plus iNO. Treatment response with the assigned therapy was defined as sustained PaO2 of 60 mm Hg or greater. RESULTS: Baseline oxygenation index and PaO2 were 48 +/- 2 and 41 +/- 1 mm Hg, respectively, during treatment with conventional ventilation. Ninety-eight patients were randomly assigned to initial treatment with HFOV, and 107 patients to iNO. Fifty-three patients (26%) recovered with the initially assigned therapy without crossover (30 with iNO [28%] and 23 with HFOV [23%]; p = 0.33). Within this group, survival was 100% and there were no differences in days of mechanical ventilation, air leak, or supplemental oxygen requirement at 28 days. Of patients whose initial treatment failed, crossover treatment with the alternate therapy was successful in 21% and 14% for iNO and HFOV, respectively (p = not significant). Of 125 patients in whom both treatment strategies failed, 32% responded to combination treatment with HFOV plus iNO. Overall, 123 patients (60%) responded to either treatment alone or combination therapy. By disease category, response rates for HFOV plus iNO in the group with respiratory syndrome and the group with meconium aspiration syndrome were better than for HFOV alone or iNO with conventional ventilation (p < 0.05). Marked differences in outcomes were noted among centers (percent death or treatment with extracorporeal membrane oxygenation = 29% to 75%). CONCLUSIONS: We conclude that treatment with HFOV plus iNO is often more successful than treatment with HFOV or iNO alone in severe PPHN. Differences in responses are partly related to the specific disease associated with PPHN.

Administration, Inhalation↗

Prone positioning decreases episodes of hypoxemia in extremely low birth weight infants (1000 grams or less) with chronic lung disease.

Extremely low birth weight infants with chronic lung disease (CLD) have frequent episodes of desaturation (hypoxemia). We quantified oxygenation and episodes of hypoxemia in 55 infants (birth weight < or = 1000 gm) with CLD in the supine versus prone position, for 1-hour time intervals. Oxygen saturation was measured with the Nellcor N-200 pulse oximeter and a computer program. Prone positioning increased oxygen saturation from 92.0% to 94.1% (p < 0.001) and significantly decreased episodes of hypoxemia to oxygen saturation levels of less than 90%, 85%, and 80% (p < 0.001). Our findings support prone positioning for the extremely low birth weight infant with CLD in an intensive care setting.

Chronic Disease↗

Effects of early dexamethasone therapy on pulmonary mechanics and chronic lung disease in very low birth weight infants: a randomized, controlled trial.

OBJECTIVE: To determine the changes in pulmonary mechanics before and during early dexamethasone therapy, and to evaluate the effect of dexamethasone on the duration of mechanical ventilation in very low birth weight (VLBW) ventilator-dependent infants at risk for chronic lung disease (CLD). METHODS: A prospective randomized trial was conducted. Forty-three patients (birth weight 600 to 1500 g, gestational age 24 to 32 weeks) who failed to be weaned from the respirator at 7 to 14 days of age were enrolled; 23 infants received a 7-day course of dexamethasone (0.5 mg/kg/day intravenously for 3 days, 0.25 mg/kg/day for 3 days, and 0.1 mg/kg/day for 1 day), and 20 patients were in the control group. At similar mean airway pressure (MAP) and fractional inspired oxygen concentration (FiO2), respiratory system mechanics were measured before and on days 2, 5, and 7 of the study. Airway pressure, flow and tidal volume (VT) were recorded and only mechanical breaths were analyzed. Respiratory compliance (Crs) and respiratory resistance (Rrs) were calculated by two factor least mean square analysis. RESULTS: Eighty-three percent of infants in the dexamethasone group and 90% in the control group received surfactant in the first 24 hours of life. There was a significant increase in Crs and VT in the dexamethasone group as compared with the control group (P < .001). No major changes in Rrs were observed. Dexamethasone therapy significantly decreased FiO2 and MAP P < .001) and facilitated successful weaning from mechanical ventilation. In addition to a shorter duration of mechanical ventilation (P < .01), the occurrence of CLD (FiO2 > 0.21 at 36 weeks of corrected gestational age, chest radiograph changes) was significantly decreased in the dexamethasone group (P < .01). Except for a transient increase in blood pressure and serum glucose, there were no significant differences in infection rates, intraventricular hemorrhage, or retinopathy of prematurity. Thirteen patients in the control group received dexamethasone at a later age. CONCLUSIONS: Our findings indicate that: 1) early dexamethasone therapy in VLBW infants markedly improves respiratory compliance and tidal volume, reduces FiO2 and MAP requirements, and facilitates extubation in these infants; 2) early dexamethasone therapy reduces the duration of mechanical ventilation and decreases CLD (at 28 days and 36 weeks) in a population of VLBW infants largely treated with surfactant.

Chronic Disease↗

Neonatal pulmonary mechanics and oxygenation after prophylactic amnioinfusion in labor: a randomized clinical trial.

OBJECTIVE: Amnioinfusion has been reported to improve the perinatal outcome of pregnancies complicated by decreased amniotic fluid volume, but detailed information on its possible adverse effects on neonatal pulmonary mechanics and oxygenation is not available. STUDY DESIGN: We evaluated 42 infants with birth weights of 2600 to 4320 g and gestational ages of 36 to 44 weeks, who were born to mothers enrolled in a prospective, randomized trial of amnioinfusion for oligohydramnios in labor. Maternal entry criteria were gestational age 36 weeks or older, estimated fetal weight more than 2500 g, oligohydramnios defined as an amniotic fluid index of 5 cm or less, and a normal fetal heart rate pattern. Evaluation of pulmonary mechanics and oxygen saturation (SaO2) was done with the infants breathing room air between birth and day 3 of life. Transpulmonary pressure, flow, and tidal volume were recorded simultaneously, and pulmonary resistance and lung compliance were calculated. SaO2 was measured for 30 minutes with the Nellcor N-200 oximeter and IBM computer oximetry software. RESULTS: Evaluation of the data revealed no significant difference between the two groups for tidal volume, lung compliance, pulmonary resistance, or work of breathing. There were no differences between the two groups in the number of desaturation episodes or in percent of desaturations to less than 90%, 85%, or 80% SaO2. CONCLUSION: Prior studies have shown amnioinfusion to improve perinatal outcome. Our findings demonstrate that amnioinfusion for oligohydramnios in labor does not adversely affect neonatal pulmonary mechanics or oxygenation.

Amnion↗

Production and characterization of a monoclonal antibody to partially purified estrogen receptor from human breast tumor.

A hybridoma cell line that secretes monoclonal antibody, MAb-ER-Br-1-15-4-18 is established. The MAb is highly specific for estrogen receptor (ER) from human breast tumor cells. In order to raise the antibody, the ER was first isolated from human breast tumor. Mice were immunized with the partially purified ER and the fusion of the spleen cells from the mouse, showing the highest serum titer, with the cells of the NS-1 mouse myeloma line, produced hybrid cells which continuously secreted antibodies specific for ER. Three of the hybridoma cultures which tested strongly positive were cloned using limiting dilution method and one of the cell lines was selected for further study. The recovery of the MAb from the cell culture was done by ammonium sulfate precipitation followed by dialysis and then hydroxylapatite liquid chromatography using linear gradients. The purity of the antibody was checked by polyacrylamide gel electrophoresis. The MAb was isotyped and found to be IgG1. When checked against other antigens the MAb showed a minimal cross-reactivity to ER from rabbit uterus and none to ovalbumin or rat liver ferritin. Further experiments showed that the MAb recognized the ER bound to the hormone and ER in the nucleus of breast tumor cells.

Antibodies, Monoclonal↗

Dexamethasone therapy in chronic lung disease.

Steroids have been used in the treatment of infants with chronic lung disease (CLD) for over a decade. Some studies have reported beneficial effects from long, tapering 42-day course of dexamethasone. Short term regimens have also shown beneficial effects on ventilator dependent infants with CLD. Although steroid therapy has been successful in infants with established CLD, more recently, dexamethasone therapy is being initiated in infants with RDS considered to be at risk for developing CLD. Some of the initial studies reported higher rates of infection, but more recent prospective data have not shown an increased incidence of sepsis in patients treated with steroids. Presently, early steroid therapy appears to be beneficial to minimize lung injury in infants treated with surfactant.

Chronic Disease↗

Pulse oximetry in newborn infants with birth weights of 620 to 4285 grams receiving dopamine and dobutamine.

The reliability of pulse oximetry in neonates receiving inotropic drugs because of hypotension and microcirculatory perfusion failure has not been well documented. Signal loss of the pulse oximeter in adult patients receiving dopamine infusions has been reported. To evaluate the relationship between pulse oximeter oxygen saturation (SaO2) and co-oximeter directly measured oxygen saturation, we studied 30 infants in the first 4 days of life (birth weight 620 to 4285 gm, gestational age 26 to 43 weeks) receiving dopamine (30 patients) and dobutamine (10 infants). Infants had normal blood pressures at the time of the study. To minimize motion artifact a Nellcor N-200 (Nellcor Incorporated, Hayward, Calif.) oximeter with electrocardiographic synchronization was used. We compared pulse oximeter values with simultaneous arterial samples analyzed for oxygen saturation with an IL 282 co-oximeter (Instrumentation Laboratory, Inc., Lexington, Mass.). The values were corrected for spuriously elevated carboxyhemoglobin levels and fetal hemoglobin level was quantitatively measured. The partial pressure of oxygen at 90% hemoglobin saturation for each patient was calculated. The dosage of dopamine ranged from 4 to 28 micrograms/kg per minute and the dosage of dobutamine varied from 4 to 24 micrograms/kg per minute. Over a wide range of values for mean blood pressure (23 to 66 mm Hg), partial pressure of oxygen at 90% hemoglobin saturation (43.1 to 70.2 mm Hg), and oxygen saturation (SaO2 80% to 100%), linear regression analysis revealed a close correlation between pulse oximeter SaO2 and co-oximeter SaO2 values (r = 0.83, standard error of the estimate 2.2%, p < 0.0001). Our findings indicate that pulse oximetry can be used reliably for continuous oxygen monitoring in normotensive neonates with an SaO2 of 80% to 100% who are receiving dopamine and dobutamine.

Birth Weight↗